The present invention is concerned with a process for dehydrogenating compounds, particularly 3-oxo-4-azasteroids, to prepare corresponding .DELTA..sup.1 compounds and novel intermediates utilized in the process.
Heretofore, azasteroids have been dehydrogenated to introduce a .DELTA..sup.1 double bond by means of benzene seleninic anhydride oxidation in which the saturated compound was heated with the benzene seleninic anhydride in refluxing chlorobenzene. Back, T. G., J. Org. Chem. 46: 1442 (1981); Rasmussen et al., J. Med. Chem. 29: 2298 (1986). Additionally, sulfoxide elimination has been a process used to accomplish the dehydrogenation. See U.S. Pat. Nos. 4,377,584, 4,220,775 and EP application 85301122.9 (published Sept.18, 1985). However, these reactions have been found to give poor yields, with a high degree of impurities and one requires the use of a selenium catalyst which is very expensive and is quite toxic.
It has also been known to dehydrogenate a 3-oxo-4-azalactam by a complicated 5 step process which involves a sulfenate intermediate. See Magnus et al., J. Am. Chem. Soc. 1986: 108 221-227. However, the process of the present invention provides a versatile single pot process for the direct introduction of a .DELTA..sup.1 double bond into 3-oxo 4 azasteroids in high yields and without the attendant toxicity and impurity problems associated with the prior art.
The process of the present invention is a single-pot silyation mediated quinone oxidation of lactams, lactones and 3-keto-4-azasteroids to the corresponding .DELTA..sup.1 double bond compound. The present invention provides a unique way to dehydrogenate a wide variety of compounds while avoiding the disadvantages of the prior art methods of affecting such transformations. The disadvantages overcome by the present invention include complicated multi step processes, poor yields, unwanted by-products and the use of toxic selenium catalysts.